G04SecL04Tpc1: Difference between revisions
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==Introduction== | ==Introduction== | ||
Spirochetes are motile, spiral shaped microorganisms. They have an inner membrane, a thin peptidoglycan layer and outer membrane and a periplasmic space. One well known characteristic of spirochetes is that they have lipoproteins that are surface-exposed on their outer membrane. (Connolly & Benach 2005). These proteins determine the ability of the antigen to trigger an immune response. In [http://en.wikipedia.org/wiki/Lyme_disease_microbiology#Outer_surface_proteins Lyme disease] the lipoproteins are outer-surface proteins. Though it has many outer-surface proteins on its outer membrane, Outer Surfafce Protein B (Osp B) and outer surface protein A (OspA) are very important lipoproteins in Lyme Disease | Spirochetes are motile, spiral shaped microorganisms. They have an inner membrane, a thin peptidoglycan layer and outer membrane and a periplasmic space. One well known characteristic of spirochetes is that they have lipoproteins that are surface-exposed on their outer membrane. (Connolly & Benach 2005). These proteins determine the ability of the antigen to trigger an immune response. In [http://en.wikipedia.org/wiki/Lyme_disease_microbiology#Outer_surface_proteins Lyme disease] the lipoproteins are outer-surface proteins. Though it has many outer-surface proteins on its outer membrane, Outer Surfafce Protein B (Osp B) and outer surface protein A (OspA) are very important lipoproteins in Lyme Disease <ref name="Becker M">PMID:15713683</ref>. They have similar structures and they both are bactericidal but they use different antibodies to lyse the bacteria. | ||
Outer surface protein B (OspB) combines with a bactericidal fab H6831 in order to kill the bacteria [http://en.wikipedia.org/wiki/Borrelia_burgdorferi ''Borrelia Burgdorferi'']. This antibody is directed towards the C-terminus and is complement-independent. This means unlike regular antibodies, it does not need to bind to complement protein in order to lyse the bacteria. The mechanism for this amazing anomaly has not yet been discovered. However, much research has been done on the particular aspects that may aid in the process. This includes various amino acid and aromatic residues. | Outer surface protein B (OspB) combines with a bactericidal fab H6831 in order to kill the bacteria [http://en.wikipedia.org/wiki/Borrelia_burgdorferi ''Borrelia Burgdorferi'']. This antibody is directed towards the C-terminus and is complement-independent. This means unlike regular antibodies, it does not need to bind to complement protein in order to lyse the bacteria. The mechanism for this amazing anomaly has not yet been discovered. However, much research has been done on the particular aspects that may aid in the process. This includes various amino acid and aromatic residues. | ||
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==Possible Mechanism of Bactericidal Properties of Antibody Bound Complex== | ==Possible Mechanism of Bactericidal Properties of Antibody Bound Complex== | ||
Although the exact mechanism of the bacterial effect of OspB and Fab H6831 complex is not know there are several hypotheses on how bacteria lysis occurs. One such hypothesis is that bacteria lysis is the direct result of oxidative reaction of singlet oxygen and water to yield hydrogen peroxide, ozone, and hydroxide radicals (Becker et al. 2005). Experiments done by Jorge Nieva and Paul Wentworth Jr of The Scripps Research Institute describe this reaction further. They suggest that this antibody-catalyzed water oxidation pathway is a property of nearly all antibodies and is similar to phagocytosis and that this may prove to be an important defense of the immune system. However, in order for phagocytosis to occur the immune system must use a complement indirect cascade initiating a membrane attack complex (Connolly and Benach 2005). In the experiments by Nieva and Wentworth they provide evidence that this oxidative reaction is independent of this compliment system. They believe that singlet oxygen acts as the substrate and binds to binding sites within the outer surface protein folds (Nieva and Wentworth 2004). A [http://en.wikipedia.org/wiki/Singlet_oxygen singlet oxygen] acts a nucleophile and attacks one water molecule to form the dihydrogentrioxide (H<sub>2</sub>O<sub>3</sub>) intermediate which then reacts to form hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) which when given an oxygen source proves to be bactericidal. Catalase prevents the reaction of hydrogen peroxide and ozone that produces hydroxide radicals which is the potential antibacterial agent | Although the exact mechanism of the bacterial effect of OspB and Fab H6831 complex is not know there are several hypotheses on how bacteria lysis occurs. One such hypothesis is that bacteria lysis is the direct result of oxidative reaction of singlet oxygen and water to yield hydrogen peroxide, ozone, and hydroxide radicals (Becker et al. 2005). Experiments done by Jorge Nieva and Paul Wentworth Jr of The Scripps Research Institute describe this reaction further. They suggest that this antibody-catalyzed water oxidation pathway is a property of nearly all antibodies and is similar to phagocytosis and that this may prove to be an important defense of the immune system. However, in order for phagocytosis to occur the immune system must use a complement indirect cascade initiating a membrane attack complex (Connolly and Benach 2005). In the experiments by Nieva and Wentworth they provide evidence that this oxidative reaction is independent of this compliment system. They believe that singlet oxygen acts as the substrate and binds to binding sites within the outer surface protein folds (Nieva and Wentworth 2004). A [http://en.wikipedia.org/wiki/Singlet_oxygen singlet oxygen] acts a nucleophile and attacks one water molecule to form the dihydrogentrioxide (H<sub>2</sub>O<sub>3</sub>) intermediate which then reacts to form hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) which when given an oxygen source proves to be bactericidal. Catalase prevents the reaction of hydrogen peroxide and ozone that produces hydroxide radicals which is the potential antibacterial agent <ref name="Nieva,J.">PMID:15130564</ref>. This oxidation reaction leads to damage in the cell wall and plasma membrance which leads to lysis of the cell which was observed through observation under an electron microscope (Nieva and Wentworth 2004). Because B. burgdorferi survives best in environments with limited oxygen and its genome does not encode for a [http://en.wikipedia.org/wiki/Catalase catalase] it may be vulnerable to this oxidative reaction (Becker et al. 2005). | ||
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==Notes== | ==Notes== | ||
===References=== | ===References=== | ||
<references /> | <references/> | ||
PMID: | |||
15130564 | |||
<ref name= | <ref name="Nieva,J.">PMID:15130564</ref> | ||
<ref | |||
<ref name=Becker M>PMID:15713683</ref> | |||
